The long term goal of this research proposal is to delineate the mechanisms by which adenovirus transforming proteins carry out their functions in lyrically infected human cells, transformed rat cells and during tumor formation in the rat. The long term objectives fall into two categories: elucidation of the mechanisms by which the adenovirus type 5 E1B oncoproteins carry out their functions within the infected or transformed cell; and exploration of the mechanisms underlying the induction of estrogen-dependent mammary fibroadenomas and fibrosarcomas by adenovirus type 9. Specific aims include: (1) Delineate the mechanism by which the adenovirus type 5 E1B-55kDa/E4-34kDa protein complex controls transport of mRNAs from the nucleus to the cytoplasm of infected cells. (2) Explore the mechanism by which the adenovirus type 5 E1B-19kDa oncoprotein blocks the induction of apoptosis by the adenovirus type 5 E1A oncoproteins. (3) Test the role of the adenovirus type 9 E1A oncoproteins in the induction of mammary tumors and explore the process of transformation by the adenovirus type 9 E1A and E1B oncogenes. This proposal is designed to explore the functions of adenovirus oncoproteins. Analysis of adenovirus gene function has contributed not only to our understanding of viral growth processes, but it also has provided important insights to mechanisms underlying cellular gene expression and growth control, mechanisms directly relevant to our understanding of oncogenesis in the human.